Severe Spaceflight-Associated Neuro-Ocular Syndrome in an Astronaut With 2 Predisposing Factors.

Importance: Understanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management. Objective: To describe a severe case of SANS associated with 2 potentially predisposing factors. Design, Setting, and Participants: Ocular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS). Exposure: Weightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut's flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 µg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort. Main Outcomes and Measures: Refraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT. Results: Cycloplegic refraction was -1.00 diopter in both eyes preflight and +0.50 - 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 µm preflight, 613 µm on FD84; left eye, 404 µm preflight, 636 µm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 µm in the right eye on FD154 and 15.0 µm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O. Conclusions and Relevance: To the authors' knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.

Causal diagramming for assessing human system risk in spaceflight.

For over a decade, the National Aeronautics and Space Administration (NASA) has tracked and configuration-managed approximately 30 risks that affect astronaut health and performance before, during and after spaceflight. The Human System Risk Board (HSRB) at NASA Johnson Space Center is responsible for setting the official risk posture for each of the human system risks and determining-based on evaluation of the available evidence-when that risk posture changes. The ultimate purpose of tracking and researching these risks is to find ways to reduce spaceflight-induced risk to astronauts. The adverse effects of spaceflight begin at launch and continue throughout the duration of the mission, and in some cases, across the lifetime of the astronaut. Historically, research has been conducted in individual risk "silos" to characterize risk, however, astronauts are exposed to all risks simultaneously. In January of 2020, the HSRB at NASA began assessing the potential value of causal diagramming as a tool to facilitate understanding of the complex causes and effects that contribute to spaceflight-induced human system risk. Causal diagrams in the form of directed acyclic graphs (DAGs) are used to provide HSRB stakeholders with a shared mental model of the causal flow of risk. While primarily improving communication among those stakeholders, DAGs also allow a composite risk network to be created that can be tracked and configuration managed. This paper outlines the HSRB's pilot process for this effort, the lessons learned, and future goals for data-driven risk management approaches.

Levels of evidence for human system risk evaluation.

NASA uses a continuous risk management process to seek out new knowledge of spaceflight-induced risk to human health and performance. The evidence base that informs the risk assessments in this domain is constantly changing as more information is gleaned from a continuous human presence in space and from ongoing research. However, the limitations of this evidence are difficult to characterize because fewer than 700 humans have ever flown in space, and information comes from a variety of sources that span disciplines, including engineering, medicine, food and nutrition, and many other life sciences. The Human System Risk Board (HSRB) at NASA is responsible for assessing risk to astronauts and communicating this risk to agency decision-makers. A critical part of that communication is conveying the uncertainty regarding the understanding of the changes that spaceflight induces in human processes and the complex interactions between humans and the spacecraft. Although the strength of evidence grades is common in the academic literature, these scores are often not useful for the problems of human spaceflight. The HSRB continues to update the processes used to report the levels of evidence. This paper describes recent updates to the methods used to assign the level of evidence scores to the official risk postures and to the causal diagrams used by the HSRB.

Updates to the NASA human system risk management process for space exploration.

This paper describes updates to NASA's approach for assessing and mitigating spaceflight-induced risks to human health and performance. This approach continues to evolve to meet dynamically changing risk environments: lunar missions are currently being designed and the ultimate destination will be Mars. Understanding the risks that astronauts will face during a Mars mission will depend on building an evidence base that informs not only how the humans respond to the challenges of the spaceflight environment, but also how systems and vehicles can be designed to support human capabilities and limitations. This publication documents updates to the risk management process used by the Human System Risk Board at NASA and includes changes to the likelihood and consequence matrix used by the board, the design reference mission categories and parameters, and the standardized evaluation of the levels of evidence that the board accepts when setting risk posture. Causal diagramming, using directed acyclic graphs, provides all stakeholders with the current understanding of how each risk proceeds from a spaceflight hazard to a mission-level outcome. This standardized approach enables improved communication among stakeholders and delineates how and where more knowledge can improve perspective of human system risks and which countermeasures can best mitigate these risks.

Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

BACKGROUND: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. METHODS: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. RESULTS: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. CONCLUSIONS: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study.

OBJECTIVE: To determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort. METHODS: National Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index. RESULTS: There were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63). CONCLUSION: No increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.

Estimating medical risk in human spaceflight.

NASA and commercial spaceflight companies will soon be retuning humans to the Moon and then eventually sending them on to Mars. These distant planetary destinations will pose new risks-in particular for the health of the astronaut crews. The bulk of the evidence characterizing human health and performance in spaceflight has come from missions in Low Earth Orbit. As missions last longer and travel farther from Earth, medical risk is expected to contribute an increasing proportion of total mission risk. To date, there have been no reliable estimates of how much. The Integrated Medical Model (IMM) is a Probabilistic Risk Assessment (PRA) Monte-Carlo simulation tool developed by NASA for medical risk assessment. This paper uses the IMM to provide an evidence-based, quantified medical risk estimate comparison across different spaceflight mission durations. We discuss model limitations and unimplemented capabilities providing insight into the complexity of medical risk estimation for human spaceflight. The results enable prioritization of medical needs in the context of other mission risks. These findings provide a reasonable bounding estimate for medical risk in missions to the Moon and Mars and hold value for risk managers and mission planners in performing cost-benefit trades for mission capability and research investments.

Carbon Dioxide Physiological Training at NASA.

INTRODUCTION: Astronauts undergo CO2 exposure training to recognize their symptoms that can arise acutely both on the ground and in spaceflight. This article describes acute CO2 exposure training at NASA and examines the symptoms reported by astronauts during training. METHODS: In a controlled training environment, astronauts are exposed to up to 8% CO2 (60 mmHg) by a rebreathing apparatus. Symptoms are reported using a standard form. RESULTS: Symptom documentation forms between April 1994 and February 2012 were obtained for 130 astronauts. The number of symptoms reported per session out of the possible 24 was related to age and sex, with those older slightly more likely to report symptoms. Women reported more symptoms on average than men (men: 3.7, women: 4.7). Respiratory symptoms (90%), flushing sensation/sweating (56%), and dizziness/feeling faint/lightheadedness (43%) were the top symptoms. Only headache reached statistical significance in differences between men (13%) and women (37%) after adjustment for multiple testing. Among those with multiple training sessions, respiratory symptoms were the most consistently reported. DISCUSSION: CO2 exposure training is an important tool to educate astronauts about their potential acute CO2 symptoms. Wide interindividual and temporal variations were observed in symptoms reported during astronaut CO2 exposure training. Headache could not be relied on as a marker of acute exposure during testing since fewer than half the subjects reported it. Our results support periodic refresher training since symptoms may change over time. Further study is needed to determine the optimal interval of training to maximize symptom recognition and inform operational decisions.Law J, Young M, Alexander D, Mason SS, Wear ML, Méndez CM, Stanley D, Meyers Ryder V, Van Baalen M. Carbon dioxide physiological training at NASA. Aerosp Med Hum Perform. 2017; 88(10):897-902.

Relationship between carbon dioxide levels and reported headaches on the international space station.

OBJECTIVE: Because of anecdotal reports of CO(2)-related symptoms onboard the International Space Station (ISS), the relationship between CO(2) and in-flight headaches was analyzed. METHODS: Headache reports and CO(2) measurements were obtained, and arithmetic means and single-point maxima were determined for 24-hour and 7-day periods. Multiple imputation addressed missing data, and logistic regression modeled the relationship between CO(2), headache probability, and covariates. RESULTS: CO(2) level, age at launch, time in-flight, and data source were significantly associated with headache. For each 1-mm Hg increase in CO(2), the odds of a crew member reporting a headache doubled. To keep the risk of headache below 1%, average 7-day CO(2) would need to be maintained below 2.5 mm Hg (current ISS range: 1 to 9 mm Hg). CONCLUSIONS: Although headache incidence was not high, results suggest an increased susceptibility to physiological effects of CO(2) in-flight.

A comparative study of space radiation organ doses and associated cancer risks using PHITS and HZETRN.

NASA currently uses one-dimensional deterministic transport to generate values of the organ dose equivalent needed to calculate stochastic radiation risk following crew space exposures. In this study, organ absorbed doses and dose equivalents are calculated for 50th percentile male and female astronaut phantoms using both the NASA High Charge and Energy Transport Code to perform one-dimensional deterministic transport and the Particle and Heavy Ion Transport Code System to perform three-dimensional Monte Carlo transport. Two measures of radiation risk, effective dose and risk of exposure-induced death (REID) are calculated using the organ dose equivalents resulting from the two methods of radiation transport. For the space radiation environments and simplified shielding configurations considered, small differences (<8%) in the effective dose and REID are found. However, for the galactic cosmic ray (GCR) boundary condition, compensating errors are observed, indicating that comparisons between the integral measurements of complex radiation environments and code calculations can be misleading. Code-to-code benchmarks allow for the comparison of differential quantities, such as secondary particle differential fluence, to provide insight into differences observed in integral quantities for particular components of the GCR spectrum.

The effect of anatomical modeling on space radiation dose estimates: a comparison of doses for NASA phantoms and the 5th, 50th, and 95th percentile male and female astronauts.

The National Aeronautics and Space Administration (NASA) performs organ dosimetry and risk assessment for astronauts using model-normalized measurements of the radiation fields encountered in space. To determine the radiation fields in an organ or tissue of interest, particle transport calculations are performed using self-shielding distributions generated with the computer program CAMERA to represent the human body. CAMERA mathematically traces linear rays (or path lengths) through the computerized anatomical man (CAM) phantom, a computational stylized model developed in the early 1970s with organ and body profiles modeled using solid shapes and scaled to represent the body morphometry of the 1950 50th percentile (PCTL) Air Force male. With the increasing use of voxel phantoms in medical and health physics, a conversion from a mathematical-based to a voxel-based ray-tracing algorithm is warranted. In this study, the voxel-based ray tracer (VoBRaT) is introduced to ray trace voxel phantoms using a modified version of the algorithm first proposed by Siddon (1985 Med. Phys. 12 252-5). After validation, VoBRAT is used to evaluate variations in body self-shielding distributions for NASA phantoms and six University of Florida (UF) hybrid phantoms, scaled to represent the 5th, 50th, and 95th PCTL male and female astronaut body morphometries, which have changed considerably since the inception of CAM. These body self-shielding distributions are used to generate organ dose equivalents and effective doses for five commonly evaluated space radiation environments. It is found that dosimetric differences among the phantoms are greatest for soft radiation spectra and light vehicular shielding.

Radioactive waste minimization at a large academic medical facility.

The University of Texas Medical Branch (UTMB) at Galveston is a large academic medical center with about 12,700 employees, 350 radioisotope research labs and 200 permitted radioactive materials users. Consequently, UTMB generates a fairly large amount of radioactive waste. The majority of this waste contains short-lived radionuclides, such as 32P, 33P, and 35S, which are held for decay and then disposed at a sanitary landfill. However, some waste, including long-lived waste and stock vials, is compacted into drums and stored in a warehouse facility, on-site, until disposal at a low-level radioactive waste (LLRW) facility. Space in the warehouse is limited but disposal is currently cost prohibitive. A reevaluation of our program was conducted to see if volumes of LLRW requiring disposal at a commercial LLRW facility could be reduced. A reevaluation of the waste streams resulted in the shifting of most of the material that was being drummed for shipment to a LLRW facility to disposal by landfill or incineration. Materials that were previously assumed to be radioactive are now being evaluated prior to disposal to determine if they may be disposed of as non-radioactive waste. Following the initial evaluation, the amount of compacted dry solids assumed to contain long-lived radionuclides was reduced. The space that was saved due to the decrease in drumming for disposal is now used to hold the increased volume of decay-in-storage material. The monetary savings will amount to about $45,000 per year. This program is currently being expanded to reduce other waste streams at the university.